Long-term observation of immunologic reconstitution after allogeneic bone marrow transplantation: differences in recovery among functional T cell subsets

A 27-year-old male with acute lymphoblastic leukemia in the first relapse received allogeneic marrow graft from an HLA-identical sister on April 28, 1978. We studied in vitro immunologic parameters such as T cell surface phenotypes, proliferative response to PHA and Con A; T cell suppressor and helper function for in vitro immunoglobulin production stimulated with pokeweed mitogen serially after the transplantation. Despite a low OKT4/OKT8 ratio for more than 5 yrs after marrow grafting, proliferative response to PHA recovered to normal 4 yrs and 9 months post-transplant. In contrast, proliferative response to Con A did not recover. T cell suppressor function induced by Con A had recovered at 3 yrs 6 months; however helper T cell function took longer to recover. These findings suggest differences in functional recovery of T cell subsets following allogeneic marrow transplantation.     

Prevention of cerebral vasospasm with OKY-046 an imidazole derivative and a thromboxane synthetase inhibitor. A preliminary co-operative clinical study

Summary The prevention of cerebral vasospasm with OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, was studied co-operatively at ten neurosurgical services. Intravenous administrations of 2, 5 or 10 /kg/minute of OKY-046 were given continuously from the earliest possible day to the 14th SAH-day to 82 pateints with ruptured cerebral aneurysm. Sixty-eight patients (83%) showed moderate to high high-density (SAH) in their initial CTs. Angiographic vasospasms were seen in 58 patients, representing 71% of all cases or 81% of the 72 cases for which angiograms were available; the vasospasms of 45 patients (55 or 63%) were moderate to severe. Symptomatic vasospasm occurred, however, only in 27 patients (33%); in 18 of those cases, moreover, the symptoms were mild or transient. The conditions of the patients at one month after the SAH were classified into 9 grades from 0 (normal) to 8 (deceased). Fifty-two patients (63%) were classified as 0 or 1, and 64 (78%) as better than 3 (possible daily life unaided). The administration of OKY-046 was proven to decrease TXB₂ in the blood.This paper emphasizes the effectiveness of the drug for symptomatic vasospasm, and supports our previous contention that cerebral microthrombosis may play an important role in the pathogenesis of cerebral vasospasm.     

Risk factors for breast cancer: A case-control study of screen-detected breast cancer in Miyagi Prefecture, Japan

We examined the associations between reproductive factors and the risk of breast cancer on the basis of information from a total of 201,363 breast cancer screening program participants in Miyagi Prefecture, Japan, during 1987-1991. A case-control study method was applied on analysis. Data on 204 breast cancer cases identified and 810 screening year-, age- and screening area-matched normal controls were extracted. After adjustment for potential confounders, a trend of decreasing risk of breast cancer with increasing number of parity was observed (p for trend=0.03). Among parous women, lactation for the last child decreased the risk of breast cancer (odds ratio (OR) = 0.61, 95% confidence interval (95% CI) 0.39–0.94). These findings were consistent with those in clinical breast cancer reported previously. When cases were divided into two age groups, younger ( 49 y.o.) and older (50 y.o. ), family history of breast cancer among mother and sisters (OR=3.51, 95% CI 1.05–11.80), and lactation for the last child (OR=0.46, 95% CI 0.25–0.84) were associated with younger age breast cancer, whereas number of parity was associated with older age breast cancer (p for trend=0.03). The results by age group suggest that different mechanisms may exist in breast cancer developing at early and late onsets.     

Inhibition of nociceptin-induced allodynia in conscious mice by prostaglandin D2

1. We recently showed that intrathecal administration of nociceptin induced allodynia by innocuous tactile stimuli and hyperalgesia by noxious thermal stimuli in conscious mice. In the present study, we examined the effect of prostaglandins on nociceptin-induced allodynia and hyperalgesia.
2. Prostaglandin D₂ (PGD₂) blocked the allodynia induced by nociceptin in a dose-dependent manner with an IC₅₀ of 26 ng kg⁻¹, but did not affect the nociceptin-induced hyperalgesia at doses up to 500 ng kg⁻¹. BW 245C (an agonist for PGD (DP) receptor) blocked the allodynia with an IC₅₀ of 83 ng kg⁻¹.
3. The blockade of nociceptin-induced allodynia by PGD₂ was reversed by the potent and selective DP-receptor antagonist BW A868C in a dose-dependent manner with an ED₅₀ of 42.8 ng kg⁻¹.
4. Glycine (500 ng kg⁻¹) almost completely blocked the nociceptin-induced allodynia. A synergistic effect on the inhibition of nociceptin-evoked allodynia was observed between glycine and PGD₂ at below effective doses.
5. Dibutyryl cyclic AMP, but not dibutyryl cyclic GMP, blocked the nociceptin-induced allodynia with an IC₅₀ of 2.9 μg kg⁻¹.
6. PGE₂, PGF_2α, butaprost (an EP₂ agonist) and cicaprost (a PGI receptor agonist) did not affect the nociceptin-induced allodynia.
7. These results demonstrate that PGD₂ inhibits the nociceptin-evoked allodynia through DP receptors in the spinal cord and that glycine may be involved in this inhibition.

     

Use of the sandwich method with an ultra-high-molecular-weight polyethylene prosthesis and Marlex mesh in sternal reconstruction: Report of a case

A 52-year-old Japanese man with a slow-growing chondroma originating from the sternal bone was referred to our hospital. A subtotal resection of the sternum was performed, hereafter termed the sandwich method, and an originally designed prosthesis made from ultra-high-molecular-weight polyethylene and Marlex mesh was used for reconstruction. The postoperative course was uneventful without any symptoms due to paradoxical movement of the chest or regional abscess, and no disturbance in the movement of the upper limbs, such as a surgical sequelae, was observed.     

Regulation of rat mesangial cell migration by platelet-derived growth factor, angiotensin II, and adrenomedullin

This study sought to determine whether platelet-derived growth factor (PDGF) and angiotensin II (AngII) stimulate migration of cultured rat glomerular mesangial cells. After finding that this was so, the effects of adrenomedullin (ADM) and cAMP-elevating agents on basal and stimulated mesangial cell migration were examined. Two isoforms of PDGF, AB and BB, stimulated migration in a concentration-dependent manner between 1 and 50 ng/ml, while the AA isoform lacked significant effect. AngII modestly but significantly stimulated migration in a concentration-dependent manner between 10(-7) and 10(-6) mol/L. Rat ADM significantly inhibited the PDGF BB- and AngII-stimulated migration in a concentration-dependent manner between 10(-8) and 10(-7) mol/L. Inhibition by rat ADM was accompanied by an increase in cellular cAMP. cAMP agonists or inducers such as 8-bromo cAMP, forskolin, and prostaglandin I2 also significantly reduced the stimulated migration. H 89, a protein kinase A (PKA) inhibitor, attenuated the inhibitory effect of ADM, and a calcitonin gene-related peptide (CGRP) receptor antagonist, human CGRP (8-37), abolished the inhibitory effects of rat ADM. These results suggest that PDGF AB and BB as well as AngII stimulate rat mesangial cell migration and that ADM can inhibit PDGF BB- and AngII-stimulated migration, at least in part through cAMP-dependent mechanisms likely to involve specific ADM receptors with which CGRP interacts. The adenylate cyclase/cAMP/PKA system may be involved in the migration-inhibitory effect of ADM in these cells.     

A gustatory cyclic nucleotide-gated channels CNGgust, is expressed in the retina

Cyclic nucleotide-gated (CNG) channels are essential proteins that contribute to the intracellular signal transduction of the senses of sight and smell. Recently, we found a novel CNG channel (CNGgust) in rat taste buds, and demonstrated its possible involvement in taste signal transduction. In the present study, we used RT-PCR and immunostaining to prove that this gustatory CNG channel is expressed in the outer segments of rat cone photoreceptor cells. The study strongly suggests that the senses of taste and sight share, at least in part, a common signal transduction pathway.     

Recurrent benign chondroblastoma at the distal end of the radius

We report a 13-year-old boy with a rapidly recurring benign chondroblastoma in the epiphysis of the distal end of the radius.     

Effects of isatin, an endogenous MAO inhibitor, on dopamine (DA) and acetylcholine (ACh) concentrations in rats

Isatin (indole-2,3-dione), an endogenous inhibitor of monoamine oxidase (MAO), has several physiological properties for stress and anxiety. We previously identified isatin in the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using gas-chromatography mass spectrometry. This study elucidated the effects of isatin on the ACh and DA levels of brain tissues in rats. Furthermore, we evaluated the effect of isatin on DA levels in a rat model of Parkinson's disease induced by Japanese encephalitis virus. Striatal ACh and DA levels significantly increased at 2 hours after isatin (50-200 mg/kg, i.p.) administration. Perfused through a microdialysis probe, isatin (10(-6)-10(-4) M) also produced a significant and concentration-dependent increase in the ACh and DA concentrations in the perfusate from the rat striatum. Furthermore, urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. Isatin (100 mg/kg, i.p.) significantly increased striatal DA levels in a rat model of Parkinson's disease. These results suggest that urinary isatin may become a diagnostic marker for the clinical severity of Parkinson's disease and that endogenous isatin, a new biological modulator, may play a role in the regulation of the brain levels of ACh by increasing the level of DA under stress.